I see that you’re still a steak lover …
Leave me alone.
Oh, c’mon, I never said you shouldn’t eat red meat, I just said that you probably shouldn’t overdo it. Actually, a new study about red meat just came out1, should I tell you about it?
Does it show that red meat is healthier than we thought?
No, but it doesn’t show that it’s unhealthier either.
Well, what is about then?
I should have known. Fine, go ahead.
Do you remember why red meat is potentially harmful?
I think so. There are chemicals in red meat that encourage the build-up of the blood vessel plaques that lead to heart attacks and strokes.
Right, but it all depends on gut bacteria.
Oh, right. Actually, I think you’d better refresh my memory.
Sure. Some of your gut bacteria use chemicals from red meat for energy.
There are a few different ones, but main one is called choline. You have a particular type of gut bacteria that take in choline and release a different chemical called TMA. The TMA goes from your intestines into your blood with the rest of your food, and then your liver converts it into yet another chemical called TMAO. It’s the TMAO that’s the problem. That’s the one that encourages the build-up of plaques.
Right, I remember now. But I’ve forgotten why TMAO encourages the build-up of plaques. What does it do?
Do you remember what plaques are?
I think so. Sometimes my ‘bad’ cholesterol – my small depleted liver fat packages – might get stuck in the cracks in my blood vessels. This is no big deal if it happens once in a while. My immune cells will break it down and my good cholesterol – my waste packages – will take the pieces back to my liver for recycling. But if too many of my small depleted liver fat packages are getting stuck too quickly and my immune cells and waste packages can’t keep up, then it all builds up into a plaque, which eventually breaks off, clogs a blood vessel, and gives me a heart attack or stroke.
Exactly, and TMAO basically makes everything stickier, so plaque build-ups are more likely to start and harder to stop2,3
So what’s in the new study?
Well, remember that none of these problems can occur without gut bacteria – if the choline never gets converted to TMA, then there is no TMA for your liver to convert to TMAO, and no TMAO to encourage the build-up of plaques.
So they figured out that they could solve the problem with antibiotics?
No, they already knew that. Antibiotics may solve the red meat problem, but they’ll end up doing you more harm than good.
Right, because gut bacteria have a lot of other important jobs.
OK, so did they find a special antibiotic that could kill only the gut bacteria that convert choline to TMA?
Oh, wait, maybe they didn’t bother with the bacteria at all and targeted the next stage of the process instead. Did they find a way to prevent the liver from converting TMA to TMAO?
Actually, they did try that.
It worked, but it had some unfortunate side effects4.
Blocking the conversion of TMA to TMAO makes people smell like fish.
What? Are you serious?
Yes, I’m serious. In fact, this wasn’t really a surprise – there are people who naturally have a mutation that prevents their liver from converting TMA to TMAO, and one of the problems that they suffer from is called ‘fish odor syndrome’.
Yikes. OK, so I guess it’s back to targeting the gut bacteria then.
Right. You were close when you suggested that the researchers might have found a special antibiotic that could kill only the choline-converting bacteria. In fact, they didn’t even have to kill the bacteria because they found a way to prevent them from converting choline to TMA.
But isn’t that basically an antibiotic?
What do you mean?
Don’t those bacteria need to convert choline to TMA to survive?
No. They do need energy, of course. But they can get it from a lot of different chemicals, and that’s exactly what the researchers took advantage of. They found another chemical that is similar to choline called DMB.
And the choline-converting bacteria can use DMB for energy?
But they don’t convert DMB to TMA?
Right. They only convert choline to TMA, they convert DMB to something else.
And that something else is less harmful than TMA?
OK, but how does that solve the problem?
Well, in theory, if you take a DMB pill before you eat your steak, then your choline-converting bacteria will be busy with the DMB when the steak arrives in your intestines, and the choline from the steak will just pass through your intestine unprocessed.
I see. Does that actually work?
It seems to work in mice. When the researchers fed mice DMB along with choline, they didn’t see any of the problems that they saw when they fed mice choline alone. But they haven’t tried it yet in humans.
Hold on, this seems too good to be true. What about the fact that my gut bacteria will always change to reflect my diet? You told me during our original conversation that people who eat a lot of red meat will have more of the choline-converting bacteria than people who don’t.
Right. The make-up of your gut bacteria depends on the energy sources that you provide to them. If a particular type of bacteria needs a particular chemical to survive and you don’t eat that chemical, then those bacteria can’t possibly survive in your gut.
Right. I remember you telling me that if a vegetarian ate a steak, they wouldn’t end up with any TMA in their blood because they don’t have any of the choline-converting bacteria.
Right. The choline-converting bacteria could never survive in the gut of someone who doesn’t eat red meat because there would never be any choline for them to use for energy.
Right, but it works the other way as well, doesn’t it? If a particular type of bacteria needs a particular chemical to survive, and I start eating more of that chemical, then I will end up with more of those bacteria, won’t I?
OK, so this DMB trick might work at first when I don’t have enough of the choline-converting bacteria to process both the DMB and the choline at the same time. But if I keep providing all of that extra energy for those bacteria, won’t I just end up with more and more of them until I do have enough to process both the DMB and the choline at the same time?
Oh, I see. Right, that’s a great question. I would have thought the same thing. But that’s not what happened, at least in the experiments with the mice. The mice that were fed both DMB and choline actually ended up with less of the choline-converting bacteria than the mice that were fed only choline.
But how is that possible?
It’s not exactly clear. Maybe DMB is a relatively inefficient source of energy that keeps the bacteria busy but provides them with a lot less energy than choline. Or maybe it’s something much more complex involving interactions between the choline-converting bacteria and other bacteria. It’s really hard to know.
This is important point. It’s pretty much impossible to know what will happen following any subtle manipulation of gut bacteria. There are too many complex factors involved and there is too much we still don’t know. We’ve learned an incredible amount about gut bacteria over the past few years, but it’s really only the tip of the iceberg. It’s going to be a long time before we can confidently predict the effects of something like the DMB trick. For now, we’re stuck with trial-and-error.
OK, but either way, the DMB trick seems to work.
Well, I think it’s fair to say that the limited testing that’s been done so far in mice looks promising.
Great. So if I can get a hold of some DMB, then I can eat as much steak as I want?
Whoa, slow down. First of all, we have no idea whether it’s safe for humans to take DMB like that. It didn’t seem to cause the mice any problems, but there are still a lot more tests that need to be done. Second of all, steak also has a lot of saturated fat, which is another thing you should probably take it easy on because it can cause inflammation, remember?
Yeah, I remember.
But, yes, in theory, if this DMB trick works, I suppose it would mean that you could eat more steak than you do now without increasing your risk of having a heart attack or a stroke.
Sounds good to me. Are there plans to test DMB in humans?
Yes, I’m sure there are.
Do they need volunteers?
Hah! I’m not sure, you could try to get in touch with them and … hey, where are you going?
Sorry, gotta run!
1. Wang, Zeneng, et al. “Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis.” Cell 163.7 (2015): 1585-1595.
2. Koeth, Robert A., et al. “Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.” Nature medicine 19.5 (2013): 576-585.
3. Zhu, Weifei, et al. “Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk.” Cell 165.1 (2016): 111-124.
4. Shih, Diana M., et al. “Flavin containing monooxygenase 3 exerts broad effects on glucose and lipid metabolism and atherosclerosis.” Journal of lipid research 56.1 (2015): 22-37.